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Biomaterials. 2008 Feb;29(6):703-8. Epub 2007 Nov 19.

The use of deoxycholic acid to enhance the oral bioavailability of biodegradable nanoparticles.

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  • 1Department of Biomedical Engineering, Yale University, 55 Prospect St., New Haven, CT 06511, USA.

Abstract

Oral delivery of nanoparticles encapsulating drugs and proteins remains a challenging route for administration due to the many barriers in the gastrointestinal tract that limit bioavailability. We hypothesized that bile salts could be used to improve the bioavailability of poly(lactide-co-glycolide) (PLGA) nanoparticles by protecting them during their transport through the gastrointestinal tract and enhancing their absorption by the intestinal epithelia. A deoxycholic acid emulsion is shown to protect PLGA nanoparticles from degradation in acidic conditions and enhance their permeability across a Caco-2 cell monolayer, an in vitro model of human epithelium. Oral administration of loaded PLGA nanoparticles to mice, using a deoxycholic acid emulsion, produced sustained levels of the encapsulant in the blood over 24-48 h with a relative bioavailability of 1.81. Encapsulant concentration was highest in the liver, demonstrating a novel means for targeted delivery to the liver by the oral route.

PMID:
18006053
[PubMed - indexed for MEDLINE]
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